Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 276
Filtrar
1.
Medicine (Baltimore) ; 103(36): e39610, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252327

RESUMEN

BACKGROUND: Obesity, a multifactorial and complex health condition, has emerged as a significant global public health concern. Integrating machine learning techniques into obesity research offers great promise as an interdisciplinary field, particularly in the screening, diagnosis, and analysis of obesity. Nevertheless, the publications on using machine learning methods in obesity research have not been systematically evaluated. Hence, this study aimed to quantitatively examine, visualize, and analyze the publications concerning the use of machine learning methods in obesity research by means of bibliometrics. METHODS: The Web of Science core collection was the primary database source for this study, which collected publications on obesity research using machine learning methods over the last 20 years from January 1, 2004, to December 31, 2023. Only articles and reviews that fit the criteria were selected for bibliometric analysis, and in terms of language, only English was accepted. VOSviewer, CiteSpace, and Excel were the primary software utilized. RESULTS: Between 2004 and 2023, the number of publications on obesity research using machine learning methods increased exponentially. Eventually, 3286 publications that met the eligibility criteria were searched. According to the collaborative network analysis, the United States has the greatest volume of publications, indicating a significant influence on this research. coauthor's analysis showed the authoritative one in this field is Leo Breiman. Scientific Reports is the most widely published journal. The most referenced publication is "R: a language and environment for statistical computing." An analysis of keywords shows that deep learning, support vector machines, predictive models, gut microbiota, energy expenditure, and genome are hot topics in this field. Future research directions may include the relationship between obesity and its consequences, such as diabetic retinopathy, as well as the interaction between obesity and epidemiology, such as COVID-19. CONCLUSION: Utilizing bibliometrics as a research tool and methodology, this study, for the first time, reveals the intrinsic relationship and developmental pattern among obesity research using machine learning methods, which provides academic references for clinicians and researchers in understanding the hotspots and cutting-edge issues as well as the developmental trend in this field to detect patients' obesity problems early and develop personalized treatment plans.


Asunto(s)
Bibliometría , Aprendizaje Automático , Obesidad , Humanos , Obesidad/epidemiología , Investigación Biomédica/métodos , Investigación Biomédica/tendencias
2.
Pharm Res ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231906

RESUMEN

PURPOSES: Size exclusion chromatography (SEC) is widely used to characterize molecular size variants of antibody drugs. However, SEC analysis is hindered by secondary interactions (or nonspecific interactions) between proteins and stationary phase packing, which result in poor column efficiency. Previous studies have reported that chaotropic salt can inhibit these interactions, but the corresponding applications of this aspect are relatively rare. Therefore, this study introduces a novel approach using sodium iodide (NaI) as a mobile-phase component in SEC and investigates the influence of the mobile-phase composition on secondary interactions. METHODS: SEC analysis was performed on one antibody-drug conjugate and four monoclonal antibodies (mAbs) using three different mobile-phase systems (i.e., sodium chloride/L-arginine hydrochloride/NaI mobile phases system) to compare the column efficiency. Subsequently, mAb-1 was used as a model to investigate the effects of these factors on secondary interactions by adjusting the ionic strength (salt concentration) and pH of the NaI mobile-phase system. RESULTS: NaI exhibits superior column efficiency performance in the SEC analysis of most products. The ionic strength will affect nonideal electrostatic and hydrophobic interaction. An appropriate ionic strength can inhibit electrostatic interactions, while an excessive ionic strength increases hydrophobic interactions. pH primarily influences electrostatic interactions. Determining the appropriate pH necessitates consideration of the isoelectric point of the protein and the pH tolerance of the column. CONCLUSIONS: In SEC analysis, using NaI as the salt component in the mobile phase reduces secondary interactions and improves column efficiency. This approach is advantageous for samples with intense secondary interactions and is a suitable alternative.

3.
J Am Chem Soc ; 146(35): 24699-24707, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39180740

RESUMEN

Modulating the basicity of alkylamines is a crucial factor in drug design. Consequently, alkylamines with a proximal amide, ester, or ketone have become privileged features in many pharmaceutical candidates. The impact of α-amino carbonyls has made the development of new methods for their preparation a continuous challenge in synthesis. Here, we describe a practical strategy that provides a modular and programmable synthesis of a wide range of α-amino carbonyls. The generality of this process is made possible by an extremely mild method to generate carbamoyl radicals, proceeding via a Lewis acid-visible-light-mediated Norrish type-I fragmentation of a tailored carboxamide reagent and intercepted through addition to in situ generated unbiased imines. Aside from the reaction's broad scope in each component, its capacity to draw on plentiful and diversely populated amine and carbonyl feedstocks is showcased through a two-dimensional array synthesis that is used to construct a library of novel, assay-ready, α-amino amides.

4.
Nano Lett ; 24(30): 9296-9301, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39037306

RESUMEN

The two-dimensional (2D) honeycomb lattice has attracted intensive research interest due to the appearance of Dirac-type band structures as the consequence of two sublattices in the honeycomb structure. Introducing strong spin-orbit coupling (SOC) leads to a gap opening at the Dirac point, transforming the honeycomb lattice into a 2D topological insulator as a platform for the quantum spin Hall effect (QSHE). In this work, we realize a 2D honeycomb-structured film with tellurium, the heaviest nonradioactive element in Group VI, namely, tellurene, via molecular beam epitaxy. We revealed the gap opening of 160 meV at the Dirac point due to the strong SOC in the honeycomb-structured tellurene by angle-resolved photoemission spectroscopy. The topological edge states of tellurene are detected via scanning tunneling microscopy/spectroscopy. These results demonstrate that tellurene is a novel 2D honeycomb lattice with strong SOC, and they unambiguously prove that tellurene is a promising candidate for a room-temperature QSHE system.

5.
Discov Oncol ; 15(1): 259, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960980

RESUMEN

Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.

6.
Plant Commun ; 5(8): 100937, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38693694

RESUMEN

The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Autofagia , Cadenas Ligeras de Clatrina , Inmunidad de la Planta , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/metabolismo , Cadenas Ligeras de Clatrina/metabolismo , Cadenas Ligeras de Clatrina/genética , Inmunidad de la Planta/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética
7.
Sci Bull (Beijing) ; 69(13): 2136-2148, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38777682

RESUMEN

Lunar exploration is deemed crucial for uncovering the origins of the Earth-Moon system and is the first step for advancing humanity's exploration of deep space. Over the past decade, the Chinese Lunar Exploration Program (CLEP), also known as the Chang'e (CE) Project, has achieved remarkable milestones. It has successfully developed and demonstrated the engineering capability required to reach and return from the lunar surface. Notably, the CE Project has made historic firsts with the landing and on-site exploration of the far side of the Moon, along with the collection of the youngest volcanic samples from the Procellarum KREEP Terrane. These achievements have significantly enhanced our understanding of lunar evolution. Building on this success, China has proposed an ambitious crewed lunar exploration strategy, aiming to return to the Moon for scientific exploration and utilization. This plan encompasses two primary phases: the first crewed lunar landing and exploration, followed by a thousand-kilometer scale scientific expedition to construct a geological cross-section across the lunar surface. Recognizing the limitations of current lunar exploration efforts and China's engineering and technical capabilities, this paper explores the benefits of crewed lunar exploration while leveraging synergies with robotic exploration. The study refines fundamental lunar scientific questions that could lead to significant breakthroughs, considering the respective engineering and technological requirements. This research lays a crucial foundation for defining the objectives of future lunar exploration, emphasizing the importance of crewed missions and offering insights into potential advancements in lunar science.

8.
Sci Adv ; 10(19): eadl2413, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728402

RESUMEN

The existence of molecular H2O and evolution of solar wind-derived water on the lunar surface remain controversial. We report that large amounts of OH and molecular H2O related to solar wind and other multiple sources are preserved in impact glasses from Chang'e-5 (CE5) lunar soil based on reflectance infrared spectroscopy and nanoscale secondary ion mass spectrometry analyses. The estimated water content contributed by impact glasses to CE5 lunar soil was ~72 ppm, including molecular H2O of up to 15 to 25 ppm. Our studies revealed that impact glasses are the main carrier of molecular H2O in lunar soils. Moreover, water in CE5 impact glasses provides a record of complex formation processes and multiple water sources, including water derived from solar wind, deposited by water-bearing meteorites/micrometeorites, and inherited from lunar indigenous water. Our study provides a better understanding of the evolution of surficial water on airless bodies and identifies potential source and storage pathways for water in the terrestrial planets.

9.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1050-1064, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658148

RESUMEN

Heterotrimeric GTP-binding protein (G-proteins) complex, which consists of Gα, Gß and Gγ subunits, plays critical roles in defense signaling. Arabidopsis genome contains only a single Gß-encoding gene, AGB1. Loss function of AGB1 in Arabidopsis results in enhanced susceptibility to a wide range of pathogens. However, the function of soybean AGB1 in immunity has not been previously interrogated. Bioinformatic analysis indicated that there are four GmAGB1 homologous genes in soybean genome, sharing homology of 86%-97%. To overcome the functional redundancy of these GmAGB1 homologs, virus-induced gene silencing (VIGS) mediated by the bean pod mottle virus (BPMV) was used to silence these four genes simultaneously. As expected, these four GmAGB1 homologous genes were indeed silenced by a single BPMV-VIGS vector carrying a conserved fragments among these four genes. A dwarfed phenotype was observed in GmAGB1s-silenced soybean plants, suggesting that GmAGB1s play a crucial role in growth and development. Disease resistance analysis indicated that silencing GmAGB1s significantly compromised the resistance of soybean plants against Xanthomonas campestris pv. glycinea (Xag). This reduced resistance was correlated with the decreased accumulation of pathogen-induced reactive oxygen species (ROS) and the reduced activation of GmMPK3 in response to flg22, a conserved N-terminal peptide of flagellin protein. These results indicate that GmAGB1 functions as a positive regulator in disease resistance and GmAGB1 is indispensable for the ROS production and GmMPK3 activation induced by pathogen infection. Yeast two hybrid assay showed that GmAGB1 interacted with GmAGG1, suggesting that an evolutionary conserved heterotrimeric G protein complex similarly functions in soybean.


Asunto(s)
Resistencia a la Enfermedad , Silenciador del Gen , Glycine max , Enfermedades de las Plantas , Glycine max/genética , Glycine max/inmunología , Glycine max/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genética , Comovirus/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/inmunología , Regulación de la Expresión Génica de las Plantas , Subunidades beta de la Proteína de Unión al GTP/genética , Subunidades beta de la Proteína de Unión al GTP/metabolismo , Subunidades beta de la Proteína de Unión al GTP/inmunología , Xanthomonas , Especies Reactivas de Oxígeno/metabolismo
10.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1065-1075, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658149

RESUMEN

Autophagy plays an essential role in recycling/re-utilizing nutrients and in adaptions to numerous stresses. However, the roles of autophagy in soybean have not been investigated extensively. In this study, a virus-induced gene silencing approach mediated by bean pod mottle virus (BPMV) was used to silence autophagy-related gene 5 (ATG5) genes in soybean (referred to as GmATG5). Our results showed that ATG8 proteins were massively accumulated in the dark-treated leaves of the GmATG5-silenced plants relative to the vector control plants (BPMV-0), indicating that autophagy pathway is impaired in the GmATG5-silenced plants. Consistent with the impaired autophagy, an accelerated senescence phenotype was observed on the leaves of the dark-treated GmATG5-silenced plants, which was not shown on the leaves of the dark-treated BPMV-0 plants. In addition, the accumulation levels of both reactive oxygen species (ROS) and salicylic acid (SA) were significantly induced in the GmATG5-silenced plants compared with that of the vector control plants (BPMV-0), indicating an activated immunity. Accordingly, the GmATG5-silenced plants exhibited significantly enhanced resistance against Pseudomonas syringae pv. glycinea (Psg) in comparison with the BPMV-0 plants. Nevertheless, the activated immunity observed in the GmATG5-silenced plant was independent of the activation of mitogen-activated protein kinase (MAPK).


Asunto(s)
Autofagia , Comovirus , Resistencia a la Enfermedad , Silenciador del Gen , Glycine max , Enfermedades de las Plantas , Glycine max/genética , Glycine max/microbiología , Glycine max/inmunología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/virología , Autofagia/genética , Comovirus/genética , Senescencia de la Planta/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Plantas/genética , Ácido Salicílico/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Plantas Modificadas Genéticamente/genética
11.
Nat Commun ; 15(1): 2098, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459034

RESUMEN

Yutu-2 rover conducted an exciting expedition on the 41st lunar day to investigate a fin-shaped rock at Longji site (45.44°S, 177.56°E) by extending its locomotion margin on perilous peaks. The varied locomotion encountered, especially multi-form wheel slippage, during the journey to the target rock, established unique conditions for a fin-grained lunar regolith analysis regarding bearing, shear and lateral properties based on terramechanics. Here, we show a tri-aspect characterization of lunar regolith and infer the rock's origin using a digital twin. We estimate internal friction angle within 21.5°-42.0° and associated cohesion of 520-3154 Pa in the Chang'E-4 operational site. These findings suggest shear characteristics similar to Apollo 12 mission samples but notably higher cohesion compared to regolith investigated on most nearside lunar missions. We estimate external friction angle in lateral properties to be within 8.3°-16.5°, which fills the gaps of the lateral property estimation of the lunar farside regolith and serves as a foundational parameter for subsequent engineering verifications. Our in-situ spectral investigations of the target rock unveil its composition of iron/magnesium-rich low-calcium pyroxene, linking it to the Zhinyu crater (45.34°S, 176.15°E) ejecta. Our results indicate that the combination of in-situ measurements with robotics technology in planetary exploration reveal the possibility of additional source regions contributing to the local materials at the Chang'E-4 site, implying a more complicated geological history in the vicinity.

12.
Plant Sci ; 343: 112057, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38460553

RESUMEN

The eukaryotic AGC protein kinase subfamily (protein kinase A/ protein kinase G/ protein kinase C-family) is involved in regulating numerous biological processes across kingdoms, including growth and development, and apoptosis. PDK1(3-phosphoinositide-dependent protein kinase 1) is a conserved serine/threonine kinase in eukaryotes, which is both a member of AGC kinase and a major regulator of many other downstream AGC protein kinase family members. Although extensively investigated in model plant Arabidopsis, detailed reports for tobacco PDK1s have been limited. To better understand the functions of PDK1s in tobacco, CRISPR/CAS9 transgenic lines were generated in tetraploid N. tabacum, cv. Samsun (NN) with 5-7 of the 8 copies of 4 homologous PDK1 genes in tobacco genome (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out. Numerous developmental defects were observed in these NtPDK1a/1b/1c/1d CRISPR/CAS9 lines, including cotyledon fusion leaf shrinkage, uneven distribution of leaf veins, convex veins, root growth retardation, and reduced fertility, all of which reminiscence of impaired polar auxin transport. The severity of these defects was correlated with the number of knocked out alleles of NtPDK1a/1b/1c/1d. Consistent with the observation in Arabidopsis, it was found that the polar auxin transport, and not auxin biosynthesis, was significantly compromised in these knockout lines compared with the wild type tobacco plants. The fact that no homozygous plant with all 8 NtPDK1a/1b/1c/1d alleles being knocked out suggested that knocking out 8 alleles of NtPDK1a/1b/1c/1d could be lethal. In conclusion, our results indicated that NtPDK1s are versatile AGC kinases that participate in regulation of tobacco growth and development via modulating polar auxin transport. Our results also indicated that CRISPR/CAS9 technology is a powerful tool in resolving gene redundancy in polyploidy plants.


Asunto(s)
Arabidopsis , Nicotiana , Nicotiana/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Sistemas CRISPR-Cas , Proteínas Quinasas/genética , Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
13.
Plant Sci ; 342: 112051, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38417717

RESUMEN

Salicylic acid (SA) is a key phyto-hormone that is essential for plant immunity. SARD1 (SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1), a member of the CBP60 (CALMODULIN-BINDING PROTEIN60) gene family, is one of the major transcription factors regulating the expression of the genes in SA biosynthesis. SARD1 has been extensively studied in model plant Arabidopsis. However, the function of SARD1 homologues in SA biosynthesis and immune responses have rarely been investigated in other plant species. In this study, the CRISPR/CAS9 (Clustered Regularly Interspersed Short Palindromic Repeats/CAS9) technology was used in creating transgenic tobacco mutant lines with 6-8 alleles of four NtSARD1 homologous genes (NtSARD1a/1b/1c/1d) knocked out. No significant difference in morphological phenotype was observed between the transgenic knockout lines and the wild type tobacco plants, indicating that knocking out NtSARD1s does not affect the growth and development in tobacco. However, knocking out or partially knocking out of NtSARD1a/b/c/d resulted in a significantly reduced expression of NtICS1, the key gene in SA biosynthesis pathway, and thus the subsequently decreased SA/SAG accumulations in response to Pst DC3000 (Pseudomonas syrangae pv.tomato DC3000) infection, indicating a key role of NtSARD1 genes in SA biosynthesis in tobacco. As a consequence of reduced SA/SAG accumulation, the Pst DC3000-induced expression of NtPR genes as well as the resistance to Pst DC3000 were both significantly reduced in these knockout lines compared with the wild type tobacco plants. Interestingly, the reductions in the SA/SAG level, NtPR gene induction and Pst DC3000 resistance were positively correlated with the number of alleles being knocked out. Furthermore, LUC reporter gene driven by the promoter of NtICS1 containing two G(A/T)AATT(T/G) motifs could be activated by NtSARD1a, suggesting that NtSARD1a could bind to the core G(A/T)AATT(T/G) motifs and thus activate the expression of LUC reporter. Taken together, our results demonstrated that the NtSARD1 proteins play essential roles in SA biosynthesis and immune responses in tobacco. Our results also demonstrated that the CRISPR/CAS9 technology can overcome gene redundancy and is a powerful tool to study gene functions in polyploid plant species.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ácido Salicílico/metabolismo , Nicotiana/genética , Sistemas CRISPR-Cas , Tetraploidía , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Enfermedades de las Plantas , Pseudomonas syringae/fisiología , Regulación de la Expresión Génica de las Plantas
14.
Natl Sci Rev ; 11(2): nwad329, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38384740

RESUMEN

As the cornerstone mission of the fourth phase of the Chinese Lunar Exploration Program, Chang'E-7 (CE-7) was officially approved, and implementation started in 2022, including a main probe and a communication relay satellite. The main probe, consisting of an orbiter, a lander, a rover and a mini-flying probe, is scheduled to be launched in 2026. The lander will land on Shackleton crater's illuminated rim near the lunar south pole, along with the rover and mini-flying probe. The relay satellite (named Queqiao-2) will be launched in February 2024 as an independent mission to support relay communication during scientific exploration undertaken by Chang'E-4, the upcoming Chang'E-6 in 2024 and subsequent lunar missions. The CE-7 mission is mainly aimed at scientific and resource exploration of the lunar south pole. We present CE-7's scientific objectives, the scientific payloads configuration and the main functions for each scientific payload with its key technical specifications.

15.
Sheng Wu Gong Cheng Xue Bao ; 40(1): 163-176, 2024 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-38258639

RESUMEN

The WRKYs are a group of plant-specific transcription factors that play important roles in defense responses. In this study, we silenced 2 GmWRKY33B homologous genes using a bean pod mosaic virus (BPMV) vector carrying a single fragment from the conserved region of the GmWRKY33B genes. Silencing GmWRKY33B did not result in morphological changes. However, significantly reduced resistances to Pseudomonas syringae pv. glycinea (Psg) and soybean mosaic virus (SMV) were observed in the GmWRKY33B-silenced plants, indicating a positive role of the GmWRKY33B genes in disease resistance. Kinase assay showed that silencing the GmWRKY33B genes significantly reduced the activation of GmMPK6, but not GmMPK3, in response to flg22 treatment. Reverse transcriptase PCR (RT-PCR) analysis of the genes encoding prenyltransferases (PTs), which are the key enzymes in the biosynthesis of glyceollin, showed that the Psg-induced expression of these genes was significantly reduced in the GmWRKY33B-silenced plants compared with the BPMV-0 empty vector plants, which correlated with the presence of the W-boxes in the promoter regions of these genes. Taken together, our results suggest that GmWRKY33Bs are involved in soybean immunity through regulating the activation of the kinase activity of GmMPK6 as well as through regulating the expression of the key genes encoding the biosynthesis of glyceollins.


Asunto(s)
Dimetilaliltranstransferasa , Glycine max , Glycine max/genética , Resistencia a la Enfermedad/genética , Bioensayo , Silenciador del Gen
16.
IUBMB Life ; 76(2): 88-100, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37596858

RESUMEN

Our hospital admitted a patient who had difficulty in coagulation even after blood replacement, and the patient had abused caffeine sodium benzoate (CSB) for more than 20 years. Hence, we aimed to explore whether CSB may cause dysfunction in vascular endothelial cells and its possible mechanism. Low, medium, and high concentrations of serum of long-term CSB intake patients were used to treat HUVECs, with LPS as the positive control. MTT and CCK8 were performed to verify CSB's damaging effect on HUVECs. The expression of ET-1, ICAM-1, VCAM-1, and E-selectin were measured by ELISA. TUNEL assay and Matrigel tube formation assay were carried out to detect apoptosis and angiogenesis of HUVECs. Flow cytometry was applied to analyze cell cycles and expression of CD11b, PDGF, and ICAM-1. Expression of PDGF-BB and PCNA were examined by western blot. The activation of MAPK signaling pathway was detected by qRT-PCR and western blot. Intracellular Ca2+ density was detected by fluorescent probes. CCK8 assay showed high concentration of CSB inhibited cell viability. Cell proliferation and angiogenesis were inhibited by CSB. ET-1, ICAM-1, VCAM-1, and E-selectin upregulated in CSB groups. CSB enhanced apoptosis of HUVECs. CD11b, ICAM-1 increased and PDGF reduced in CSB groups. The expression level and phosphorylation level of MEK, ERK, JUN, and p38 in MAPK pathway elevated in CSB groups. The expression of PCNA and PDGF-BB was suppressed by CSB. Intracellular Ca2+ intensity was increased by CSB. Abuse of CSB injured HUVECs and caused coagulation disorders.


Asunto(s)
Selectina E , Molécula 1 de Adhesión Intercelular , Humanos , Células Endoteliales de la Vena Umbilical Humana , Células Cultivadas , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Selectina E/metabolismo , Benzoato de Sodio/metabolismo , Benzoato de Sodio/farmacología , Becaplermina/farmacología , Cafeína/metabolismo , Cafeína/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo
17.
Rheumatol Ther ; 11(1): 97-112, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37982966

RESUMEN

INTRODUCTION: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. METHODS: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). RESULTS: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. CONCLUSION: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

18.
J Agric Food Chem ; 72(1): 516-528, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38130104

RESUMEN

Pterostilbene, a derivative of resveratrol, is of increasing interest due to its increased bioavailability and potential health benefits. Sustainable production of pterostilbene is important, especially given the challenges of traditional plant extraction and chemical synthesis methods. While engineered microbial cell factories provide a potential alternative for pterostilbene production, most approaches necessitate feeding intermediate compounds. To address these limitations, we adopted a modular coculture engineering strategy, dividing the pterostilbene biosynthetic pathway between two engineered E. coli strains. Using a combination of gene knockout, atmospheric and room-temperature plasma mutagenesis, and error-prone PCR-based whole genome shuffling to engineer strains for the coculture system, we achieved a pterostilbene production titer of 134.84 ± 9.28 mg/L from glucose using a 1:3 inoculation ratio and 0.1% dimethyl sulfoxide supplementation. This represents the highest reported de novo production titer. Our results underscore the potential of coculture systems and metabolic balance in microbial biosynthesis.


Asunto(s)
Escherichia coli , Glucosa , Escherichia coli/genética , Escherichia coli/metabolismo , Glucosa/metabolismo , Técnicas de Cocultivo , Barajamiento de ADN , Vías Biosintéticas , Ingeniería Metabólica/métodos
19.
Angew Chem Int Ed Engl ; 63(7): e202312354, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38133603

RESUMEN

The achievement of directly activating and utilizing bulk small molecules has remained a longstanding objective in the field of chemical synthesis. The present work reports a catalytic activation method for bulk chemical nitromethane (MeNO2 ). This method combines homogeneous Lewis acid with recyclable heterogeneous Brønsted acid catalysis, featuring practicality, sustainability, and low cost, thus solving the inherent drawbacks of previous Nef processes where stoichiometric reductants or activators were required. By combining the advantages of both homo- and heterogeneous catalysts, this chemistry may not only offer new opportunities for the further development of MeNO2 as a nitrogen source for organic synthesis, but also promote the catalysis design in synthetic chemistry.

20.
ACS Omega ; 8(50): 47938-47953, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38144124

RESUMEN

The Ediacaran Doushantuo phosphate deposit in Kaiyang, Guizhou Province, China, contains thick phosphate ores. Most of the ores are reconstituted phosphorite, and there have been few studies of the primary phosphorites, which has led to controversy regarding the origins and nature of mineralization of these phosphate-rich deposits. We identified high-grade primary phosphorites in the Kaiyang area and undertook a stratigraphic, petrological, sedimentological, geochemical, and isotopic study of these rocks. Moving up-section, the Longshui phosphate ore deposit comprises granular, micritic, stromatolitic, honeycomb, and sandy phosphorites. The first four types of phosphorite contain abundant biological structures, such as spherical, lobe-like, and amorphous forms. These are mainly fossils of benthic multicellular red algae, along with other types of algae. These fossils comprise >70% of the phosphorites, indicating that these are protist phosphorites. The ores are massive, unstratified, and contain numerous layered cavity structures, indicating that the ore bed was originally a reef. The phosphorites have P2O5 contents of 38.6-40.2 wt %, with an average of 38.9 wt %. The Al2O3 + TiO2 values are 0.02-0.44 wt %. The δ18O values of the samples vary from 13.76 to 16.57‰, with an average of 14.60‰, and δ13C values range from -15.789 to -8.697‰, with an average of -13.133‰. The samples exhibit rare-earth element patterns that are enriched with middle rare-earth elements and have strongly negative Ce anomalies. The geochemical features show that the reef was deposited in clear and oxidized waters. The discovery of this high-grade protist phosphorite shows that the involvement of algae was key to the formation of the Kaiyang phosphate-rich deposit.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA